PATHO: PSYCHOBIOLOGY EXEMPLARS

what is psychobiology associated with

• Cognition

• Psychosis

• Mood & Affect

• Anxiety

• all have a close link with stress and coping

anxiety

Sense of dread without any apparent stimulus

what does anxiety lead to

negative coping mechanisms

common symptom of anxiety

avoidance

• avoidance of social interactions, relationships, opportunities for growth

anxiety somatic responses

palpitations, sweating, rapid breathing

• SNS epi and noepi being released

possible causes of anxiety

• Traumatic events and stress

• Genetic influences

• neurotransmitters

• stress/ HPA

what neurotransmitters are involved in anxiety

GABA – decreased receptors in amygdala and hippocampus

• May be decrease in serotonin as well

anxiety stress and HPA

• Norepinephrine – inappropriate activation of NE system in locus coeruleus

• Imbalance between NE and other neurotransmitter systems (dopamine, glutamate, cortisol releasing hormone)

memory involvement and anxiety

consolidation and re-consolidation

consolidation

occurs in amygdala, memories of fearful stimuli are stored

Re-consolidation

process by which an older memory is activated and reinforced. When cues recall a fear memory, it becomes part of new experience, part of long- term memory, makes fear memories even stronger

• neuronal circuit strengthens with each firing

brain involvement in anxiety

Caudate nucleus

amygdala

modulating factors

Caudate nucleus and anxiety

drives behavior based on recall of past successful outcomes; if this area does not function well, recall is impaired and only negative aspects are focused on

amygdala and anxiety

hyperreactive or hyperresponsive in anxiety (memory)

modulating factors and anxiety

modulating factors in brain that turn down the stress response may not be working correctly

Obsessive-Compulsive Disorder

Recurring unwanted thoughts, ideas, or sensations (obsessions) that make them feel driven to do something repetitively (compulsions)

OCD neurotransmitters

• Decrease in serotonin

• Increase in cortisol

OCD brain involovement

Prefrontal cortex

frontal lobe activity

basal ganglia

Prefrontal cortex and OCD

overactive circuits fail to integrate cognitive and emotional responses to sensory input; rumination

increased frontal lobe activity and ODC

guilt, intense affect, worry

basal ganglia abnormalities and OCD

can lead to difficulty with processing emotions and memories

Generalized Anxiety Disorder (GAD)

state of excessive worrying that interferes with daily function

Generalized Anxiety Disorder manifestations

• Worry generates restlessness, fatigue, irritability, tension – cognitive symptoms

• Considered a worry-centered anxiety disorder, “free-floating” anxiety

• Avoidance is common

• Can evolve into OCD or phobias

GAD neurotransmitters

Increased norepinephrine (exciting) and decreased levels of GABA (inhibitory)

GAD and brain involvement

Limbic system and midbrain involved including amygdala and hippocampus – alteration of processing stressful memories

Post-Traumatic Stress Disorder

•Initial traumatic event – either directly experienced or witnessed

•Beyond the “realm of normal human experience”

PTSD neurotransmitters

decrease in GABA

PTSD manifestations

•Memory disorder (flashbacks, intrusive thoughts, impaired memory)

•Cognition symptoms (difficulty concentrating, hypervigilence)

•Physical sypmtoms (sleep disturbances, somatic problems)

PTSD brain involovement

•Hyper-responsiveness of the amygdala occurs – contributes to suicidal thoughts

•Consolidation-reconsolidation abnormalities

•Hippocampus - flashbacks

PTSD has a high rate of

suicide

panic disorder

sudden episodes of intense fear

panic disorder manifestation

• Increased sympathetic function; palpitations, sweating, feelings of unreality, avoidance of situation

• Numbness, parasthesias

• Feeling of impending doom

what is panic disorder considered

a “fear-centered” anxiety disorder

“fear-centered” anxiety disorder

episodes may occur following a situation mind associates with negative consequences or random situation

Panic disorder Neurotransmitters

• Increase in norepinephrine due to fight or flight response;

• Decreased GABA

• Increased glutamate

panic disorder trigger

caffeine

panic disorder brain involovement

• Hippocampus

• Limbic system (includes hypothalamus, amygdala, and hippocampus)

• Prefrontal cortex

what can develop as a result of panic disorder

phobias → specific trigers can lead to panic attacks

what disorder is depression

mood diorder

depression comorbidity

anxiety

what does depression have a serious negative impact on

functioning and relationships

depression

Persistent feelings of sadness and loss of interest in life

major depressive disorder

symptoms lasting 2 weeks or longer

who does depression impact

all races, genders, and people in all socioeconomic classes

what exacerbates symptoms of depression

stress

how is depression diagnosed

At least 5 sympotoms are present during 2-week time period:

emotional symptoms of depression

Depressed mood

Markedly diminished interest or pleasure in usual activities

Significant weight loss

Insomnia or hypersomnia

Psychomotor changes (increased or decreased)

Fatigue

Feelings of worthlessness or guilt

Diminished ability to think or concentrate

Recurrent thoughts of death or suicide

physical symptoms

Sleep disturbances - REM abnormalities

Appetite disturbances

Libido disturbances

Lethargy

Body aches & pains

Headaches

Muscle pains

cause of depression

Cause is multifactorial and somewhat unknown

• Genetic component – family history

• Chronic illness

• Chronic stress

brain implications of depression

• Normally, incoming stimuli triggers an emotion and then compared to past experiences; individual processes situation

• This process does not work well in patients with depression

• Neural mechanisms that filter info become biased in favor of negative information

• Amygdala – suicidal ideations

• Stress and HPA axis – primes body for flight or fight

• Under continual stress, negative feedback receptors are desensitized

• Cortisol and CRF levels high in those with depression

• Interacts with serotonin and norepinephrine

depression neurotransmitter

• Norepinephrine – deficiency results in attending to negative emotions; linked to apathy, fatigue

• Serotonin – essential in keeping NE at appropriate level; decreased contributes to decreased mood, lack of optimism

• Dopamine – not as well understood, may be decreased in depression

mania

persistently elevated or irritable mood and increased energy; flight of ideas, delusions/hallucinations may occur; follows emotional trigger

hypomania

symptoms not as severe, patient may not notice change but others close to patient do

rapid cycling

four or more depressive and/or manic episodes within 12 months

Bipolar l

one or more manic episodes accompanied by major depressive episodes

bipolar ll

one or more major depressive episodes accompanied at least one hypomanic episode

cyclothymic

alternating periods of hypomanic and depressive symptoms not significant enough to meet criteria for mania or depression

bipolar brain implications

Prefrontal cortex – smaller and has decreased functioning (focusing attention, anticipating events, impulse control and managing emotional reactions, adjusting complex behaviors)

bipolar disorder risk facots

• Genetic implications – family history is strongest predictor

• Stressful life events (suicide of family member, etc.)

bipolar neaurotransmitter implications

Increased levels of norepinephrine - mania

bipolar causes a change in neurotransmitter

receptor sensitivity

bipolar noepi

• Excessive NE in mania

• Depleted NE in depression

bipolar neurotrnsmitter dysregulation

of serotonin and dopamine systems

bipolar and low energy strores

inhibit the process of pumping glutamate back into glial cells

Low energy stores inhibit the process of pumping glutamate back into glial cells causes…

• Glutamate excitotoxicity

• Increased risk of apoptosis in brain

• Kindling occurs

Schizophrenia

Breakdown in relationships between thought, emotion, and behavior

• spilt mind

Schizophrenia manifestations

• Faulty perceptions of world around thm

• Inappropriate actions and feelings

• Disconnect from reality

• Delusions

• Hallucinations

Delusions

fixed beliefs not based in reality

Hallucinations

perceptions without an external stimulus; hearing voices not present

Schizophrenia phase: premorbid

symptoms not showing yet

Schizophrenia phase: prodromal

gradual behavior changes

Schizophrenia phase: acute onset

worsening behavior changes (positive/above baseline symptoms)

Schizophrenia phase: progressive

may recover from first event well

Schizophrenia phase: chronic

negative/below baseline symptoms

• deteriortation over long periods of time

what can schizophrenia cause

long term disability

Schizophrenia hypothesis

First and Second Hit

Schizophrenia hypothesis: first hit

Developmental defect(s) in neuron formation and/or migration and synapse formation sensitizes the brain to react differently than a “normal” brain to later stresses (either biological or environmental)

Schizophrenia hypothesis: second hit

Stress during adolescence triggers abnormal response within brain that initiates and perpetuates injury and concurrent psychosis.

• problems with GABA transmission

Schizophrenia risk factors

• Genetic influences – connection with other neurodevelopmental disorders such as autism

• Often occur with other mental illness diagnoses

• Family history

• Childhood trauma

schizophrenia neurotransmitter implications

• Norepinephrine

• Serotonin

• GABA

• Dopamine imbalance – can contribute to language issues

schizophrenia and immune function impairment

increased levels of cytokines, illness and stress may contribute to exacerbations

Schizophrenia brain implications

• Enlarged ventricles brain tissue decrease

• Widened sulci and fissures

• Decreased cerebral cortical volume particularly in temporal and frontal lobes – leads to negative symptoms later in disease

• Volume reductions sometimes seen in hippocampus, amygdala, basal ganglia and thalamus – can contribute to behaviors including increased aggression

• Reduction in left-right temporal lobe asymmetry

• Hallucinations – abnormalities in specific areas (i. e., occipital lobe alternations – visual hallucinations)

Schizophrenia: positive symptoms

additions to normal experiences

delusions

halluncinations

abnormal movements

formal though disorder

Schizophrenia: negative symptoms

diminished affects and behaviors

flat or blunted affect

thought blocking

avolition

poverty of speech

social withdrawal

Schizophrenia: cognitive symptoms

memory deficits

attention deficis

language difficulties

loss of executive function

opioid use disorder

Recurrent use of substance such that the individual experiences clinical and functional impairment and inability to manage responsibilities of daily life

addiction

compulsive drug taking despite desire to discontinue use of drug

binge and intoxication

increased release of dopamine; activation of brain’s reward system

preoccupation

decreased function of prefrontal cortex

withdrawl

increased sensitivity to stress and negative emotions

addiction concepts

binge

intoxication

preoccupation

withdrawl

addiction brain implications

• Excess dopamine released and person feels pleasure (reward pathway)

• Increased levels of exhilaration, pleasure

• Over time - Nucleus accumbens and amygdala -pathologically altered (positive memory re-inforced)

• Dissatisfaction occurs without drug

• Repeated use – drug doesn’t cause same effect (tolerance)

addiction withdrawal

physical dependence

alcool use disorder increases…

risk to other diseases

• cancer, liver disease, cognitive dysfunction

alcohol use disorder neurotransmitter implications

• Alcohol enhances effects of GABA, decreases excitatory neurotransmitter glutamate

• Decreased GABA secreted in brain

• Increases dopamine in reward center

• When drug removed, rebound overstimulation and nervousness

what does alcohol use disorder disrupts

REM sleep

alcohol use disorder withdrawl

tremors, hallucinations, seizures

Tobacco use disorder

-Harmful consequences of persistent tobacco use, physiologic dependance

-addiction to nicotine

when tobacco is inhaled

the chemicals are rapidly absorbed in pulmonary circulation → circulated to brain

what does tobacco bind to

nicotinic cholinergic receptors, links to dopaminergic reward center